Summary: Energy strain in three-dimensional protein structures
Vladimir Maiorov and Ruben Abagyan
Background: Steric strain in protein three-dimensional structures is related to
unfavorable inter-atomic interactions. The steric strain may be a result of
packing or functional requirements, or may indicate an error in the coordinates
of a structure. Detailed energy functions are, however, usually considered too
noisy for error detection.
Results: After a short energy refinement, a full-atom, detailed energy function
becomes a sensitive indicator of errors. The statistics of the energy distribution
of amino acid residues in high-resolution crystal structures, represented by
models with idealized covalent geometry, were calculated. The interaction
energy of each residue with the whole protein structure and with the solvent
was considered. Normalized deviations of amino acid residue energies from
their average values were used for detecting energy-strained and, therefore,
potentially incorrect fragments of a polypeptide chain. Protein three-dimensional
structures of different origin (X-ray crystallography, NMR spectroscopy,
theoretical models and deliberately misfolded decoys) were compared.
Examples of the applications to loop and homology modeling are provided.
Conclusions: Elevated levels of energy strain may point at a problematic
fragment in a protein three-dimensional structure of either experimental or